BMS-986489 + Nivolumab vs Durvalumab for Small Cell Lung Cancer

(TIGOS-LS Trial)

Recruiting at 15 trial locations

Overseen By Sarah Cannon Development Innovations, LLC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: SCRI Development Innovations, LLC

Must be taking: Platinum, Etoposide

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Heart conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

250 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, randomized study of BMS-986489 (atigotatug + nivolumab fixed-dose combination) vs durvalumab in limited-stage (LS)-small-cell lung cancer (SCLC) participants. The main goals of this study are to: * Evaluate the efficacy of BMS-986489 vs durvalumab * Evaluate the safety profile of BMS-986489

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not be on chronic immunosuppressive medications or systemic corticosteroids above a certain dose. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Durvalumab for treating small cell lung cancer?

Research shows that Durvalumab, when combined with other treatments like platinum-etoposide, improved overall survival in patients with extensive-stage small-cell lung cancer, suggesting its potential effectiveness in similar conditions. ^{1 2 3 4 5}

Is the combination of BMS-986489 and Nivolumab safe for humans?

Durvalumab, a drug similar to BMS-986489, has been studied for safety in various cancers. It generally shows acceptable safety, but some patients experience serious side effects like reduced appetite and diarrhea. Safety data for BMS-986489 specifically is not available in the provided research. ^{1 2 6 7 8}

How does the drug BMS-986489 + Nivolumab differ from Durvalumab for small cell lung cancer?

The combination of BMS-986489 and Nivolumab is unique because it involves a novel drug (BMS-986489) paired with Nivolumab, a PD-1 inhibitor, which may offer a different mechanism of action compared to Durvalumab, a PD-L1 inhibitor. This combination could potentially provide a new approach to targeting the immune system in small cell lung cancer. ^{1 2 3 9 10}

Research Team

Melissa Johnson, MD

Principal Investigator

SCRI Development Innovations, LLC

Eligibility Criteria

This trial is for adults with small-cell lung cancer who've finished chemo and radiotherapy without the disease getting worse. They must have good blood and organ function, be willing to use birth control, and have a performance status showing they're mostly active.

Inclusion Criteria

I agree to follow the study's birth control rules.

I may have brain radiation to prevent cancer spread, done 14-42 days before starting the study treatment.

I am fully active or restricted in physically strenuous activity but can do light work.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiotherapy

Participants receive concurrent chemotherapy and radiotherapy according to standard guidelines for treatment of LS-SCLC

6-8 weeks

Consolidation Therapy

Participants receive either BMS-986489 (atigotatug + nivolumab) or durvalumab as consolidation therapy

Up to 3 years

Every 2 cycles (8 weeks) for the first 6 months, then every 3 cycles (12 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 8 weeks for participants who stopped treatment before disease progression and before completing 6 months of treatment and every 12 weeks for participants who stopped treatment before disease progression

Treatment Details

Interventions

• BMS-986489
• Durvalumab

Trial Overview The study compares BMS-986489 (a combination of atigotatug + nivolumab) with durvalumab in patients with limited-stage small-cell lung cancer. It's an open-label trial, meaning everyone knows which treatment they receive.

Participant Groups

Group I: BMS-986489 (atigotatug + nivolumab) Experimental Treatment 1 Intervention

Participants will receive a fixed dose of BMS-986489 (atigotatug + nivolumab) intravenously each cycle. Cycles will be 28 days. Up to 125 participants will be enrolled into this arm.

Group II: Durvalumab Active Control 1 Intervention

Participants will receive standard of care Durvalumab intravenously each cycle. Cycles will be 28 days. Up to 125 participants will be enrolled into this arm.

Who Is Running the Clinical Trial?

SCRI Development Innovations, LLC

Lead Sponsor

Trials

193

Recruited

13,800+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

In a phase 2 trial involving 444 patients with advanced non-small-cell lung cancer (NSCLC), durvalumab (an anti-PD-L1 treatment) showed a response rate of 30.9% in patients with ≥90% PD-L1 expression, indicating its potential efficacy in heavily pretreated cases.

The safety profile of durvalumab was consistent with other similar treatments, with 9% of patients experiencing grade 3 or 4 treatment-related adverse events, suggesting it is manageable and generally safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Garassino, MC., Cho, BC., Kim, JH., et al.[2022]

In the phase II ATLANTIC study, durvalumab demonstrated encouraging overall survival (OS) rates in heavily pretreated patients with advanced non-small cell lung cancer (NSCLC), with median OS ranging from 9.3 to 13.3 months depending on tumor characteristics.

The safety profile of durvalumab remained consistent with previous reports, showing no new safety concerns, indicating it is a tolerable treatment option for patients with advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final overall survival and safety update for durvalumab in third- or later-line advanced NSCLC: The phase II ATLANTIC study. Garassino, MC., Cho, BC., Kim, JH., et al.[2021]

In a phase II trial involving 116 patients with squamous non-small-cell lung cancer, durvalumab demonstrated a 16% overall response rate and a disease control rate of 54%, indicating its potential effectiveness as a treatment after platinum-based chemotherapy.

The treatment was associated with a median overall survival of 11.6 months and a median progression-free survival of 2.9 months, with 32% of patients experiencing grade ≥ 3 treatment-related adverse events, suggesting that while durvalumab is active, it also carries a risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SWOG S1400A (NCT02154490): A Phase II Study of Durvalumab for Patients With Previously Treated Stage IV or Recurrent Squamous Cell Lung Cancer (Lung-MAP Sub-study). Borghaei, H., Redman, MW., Kelly, K., et al.[2022]

In the CASPIAN trial, first-line treatment with durvalumab plus platinum-etoposide significantly improved overall survival in patients with extensive-stage small cell lung cancer, showing consistent benefits regardless of PD-L1 expression or tissue tumor mutational burden status.

The study found that while PD-L1 expression may be a useful biomarker for treatment response, the overall survival benefit of durvalumab plus EP was similar across different PD-L1 subgroups, indicating that this treatment could be effective for a broad range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab ± tremelimumab + platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): outcomes by PD-L1 expression and tissue tumor mutational burden. Paz-Ares, L., Garassino, MC., Chen, Y., et al.[2023]

In a study of 421 patients with stage III nonsmall-cell lung cancer (NSCLC) who completed chemoradiation, 76.5% initiated adjuvant durvalumab, indicating a strong uptake of this treatment in real-world settings.

The initiation of adjuvant durvalumab increased significantly over time, from 66% to 92%, suggesting that it has been rapidly integrated into clinical practice, particularly among patients with better performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uptake of Adjuvant Durvalumab After Definitive Concurrent Chemoradiotherapy for Stage III Nonsmall-cell Lung Cancer. Bryant, AK., Yin, H., Schipper, MJ., et al.[2023]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

Durvalumab, an immune checkpoint inhibitor, has shown promising efficacy in treating advanced non-small cell lung cancer (NSCLC) in early phase trials, demonstrating a good safety profile.

The PACIFIC trial has successfully met its primary endpoint, indicating that durvalumab may be an important part of future treatment strategies for NSCLC, with ongoing studies potentially confirming its superiority over current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI 4736 (durvalumab) in non-small cell lung cancer. Jeanson, A., Barlesi, F.[2021]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Final overall survival and safety update for durvalumab in third- or later-line advanced NSCLC: The phase II ATLANTIC study. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

SWOG S1400A (NCT02154490): A Phase II Study of Durvalumab for Patients With Previously Treated Stage IV or Recurrent Squamous Cell Lung Cancer (Lung-MAP Sub-study). [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Durvalumab ± tremelimumab + platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): outcomes by PD-L1 expression and tissue tumor mutational burden. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Uptake of Adjuvant Durvalumab After Definitive Concurrent Chemoradiotherapy for Stage III Nonsmall-cell Lung Cancer. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

SAKK 19/17: safety analysis of first-line durvalumab in patients with PD-L1 positive, advanced nonsmall cell lung cancer and a performance status of 2. [2021]

9. England pubmed.ncbi.nlm.nih.gov

MEDI 4736 (durvalumab) in non-small cell lung cancer. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]